Factors affecting the decline in incidence of diabetes in the Diabetes Prevention Program Outcomes Study (DPPOS)

Abstract

During the first 7 years of the Diabetes Prevention Program Outcomes Study (DPPOS), diabetes incidence rates, when compared with the Diabetes Prevention Program (DPP), decreased in the placebo (-42%) and metformin (-25%), groups compared with the rates in the intensive lifestyle intervention (+31%) group. Participants in the placebo and metformin groups were offered group intensive lifestyle intervention prior to entering the DPPOS. The following two hypotheses were explored to explain the rate differences: "effective intervention" (changes in weight and other factors due to intensive lifestyle intervention) and "exhaustion of susceptible" (changes in mean genetic and diabetes risk scores). No combination of behavioral risk factors (weight, physical activity, diet, smoking, and antidepressant or statin use) explained the lower DPPOS rates of diabetes progression in the placebo and metformin groups, whereas weight gain was the factor associated with higher rates of progression in the intensive lifestyle intervention group. Different patterns in the average genetic risk score over time were consistent with exhaustion of susceptibles. Results were consistent with exhaustion of susceptibles for the change in incidence rates, but not the availability of intensive lifestyle intervention to all persons before the beginning of the DPPOS. Thus, effective intervention did not explain the lower diabetes rates in the DPPOS among subjects in the placebo and metformin groups compared with those in the DPP.

Trial registration: ClinicalTrials.gov NCT00004992 NCT00038727.

Figure 1

Average annual incidence rates (per 100 person-years [PY]) by time since randomization by initial treatment group.

Figure 2

HRs for the DPPOS to DPP time period, by treatment group using sequential adjustment for risk factors. CES-D, Center for Epidemiologic Studies of Depression score; % CHO, percentage of calories from carbohydrate; ETOH, alcohol intake; % fat, percentage of calories from fat; goals, number of five study goals met; waist, waist circumference; % PRO, percentage of calories from protein; smoking, current, former, never cigarette smoker; SSRI, selective serotonin reuptake inhibitors; statin, HMG-CoA reductase inhibitors; TDC, time-dependent covariate; leisure, leisure time physical activity. Model 1 is unadjusted; model 2 is model 1 plus the factors listed.

Figure 3

Mean baseline GRS (top panel), baseline fasting plasma glucose level (middle panel), and baseline 2-h plasma glucose level (bottom panel) at each visit among groups of persons remaining nondiabetic at each visit.

Figure 4

A: Mean DRS at randomization by month of randomization, by treatment group (mean, 95% CIs). Each time interval includes 1,072, 1,073, and 1,075 participants, respectively, balanced in the three treatment groups. B: Mean GRS. Each time interval includes 947, 941, and 955 participants, respectively, also well balanced in the three treatment groups.